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1.
Am J Transplant ; 18(8): 1924-1935, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29734498

RESUMEN

The Organ Procurement and Transplantation Network monitors progress toward strategic goals such as increasing the number of transplants and improving waitlisted patient, living donor, and transplant recipient outcomes. However, a methodology for assessing system performance in providing equity in access to transplants was lacking. We present a novel approach for quantifying the degree of disparity in access to deceased donor kidney transplants among waitlisted patients and determine which factors are most associated with disparities. A Poisson rate regression model was built for each of 29 quarterly, period-prevalent cohorts (January 1, 2010-March 31, 2017; 5 years pre-kidney allocation system [KAS], 2 years post-KAS) of active kidney waiting list registrations. Inequity was quantified as the outlier-robust standard deviation (SDw ) of predicted transplant rates (log scale) among registrations, after "discounting" for intentional, policy-induced disparities (eg, pediatric priority) by holding such factors constant. The overall SDw declined by 40% after KAS implementation, suggesting substantially increased equity. Risk-adjusted, factor-specific disparities were measured with the SDw after holding all other factors constant. Disparities associated with calculated panel-reactive antibodies decreased sharply. Donor service area was the factor most associated with access disparities post-KAS. This methodology will help the transplant community evaluate tradeoffs between equity and utility-centric goals when considering new policies and help monitor equity in access as policies change.


Asunto(s)
Asignación de Recursos para la Atención de Salud/normas , Trasplante de Riñón/mortalidad , Asignación de Recursos/tendencias , Donantes de Tejidos/provisión & distribución , Obtención de Tejidos y Órganos/tendencias , Listas de Espera/mortalidad , Adulto , Cadáver , Femenino , Estudios de Seguimiento , Humanos , Fallo Renal Crónico/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Sistema de Registros , Tasa de Supervivencia , Receptores de Trasplantes
2.
Am J Transplant ; 17(10): 2696-2704, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28556492

RESUMEN

The Kidney Donor Profile Index (KDPI) became a driving factor in deceased donor kidney allocation on December 4, 2014, with the implementation of the kidney allocation system (KAS). On April 20, 2016, the annual recalibration of the Kidney Donor Risk Index into KDPI was incorrectly programmed in DonorNet, resulting in erroneously high KDPI values, by between 1 and 21 percentage points (e.g. actual KDPI of 70% was displayed as 86%). The error was corrected on May 19, 2016, <24 h after being recognized. During this 30-day period, the distribution of recipients largely resembled pre-KAS patterns. The observed discard rate of 22.9% was higher than the post-KAS average of 19.6% (odds ratio [OR]: 1.22) but far lower than the projected rate of 31.4% (OR: 1.96) based on the usual discard rate by KDPI relationship, suggesting clinicians and patients did not rely heavily on this single number (KDPI) in kidney-utilization decisions. Still, risk-adjusted analyses suggest the elevated discard rate was most likely attributable to the erroneously high KDPIs, not a shift in donor characteristics or random chance. The rise in discard rate was sharply higher for kidneys with inflated KDPI that crossed the 85% policy threshold (OR: 1.46; p = 0.049) versus those that did not (OR: 1.06; p = 0.631).


Asunto(s)
Trasplante de Riñón , Donantes de Tejidos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obtención de Tejidos y Órganos
3.
Am J Transplant ; 17(4): 1103-1111, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-27805305

RESUMEN

This study investigated the early effects of the new kidney allocation system (KAS) on the access of prior living kidney donors (PLDs) to deceased donor kidney transplants. Using data from the Organ Procurement and Transplantation Network, we compared prevalent and incident cohorts of PLDs in the 1-year periods before and after KAS implementation (pre-KAS group: December 4, 2013, to December 3, 2014, n = 50 [newly listed PLDs]; post-KAS group: December 4, 2014, to December 3, 2015, n = 39). We assessed transplant rates per active patient-year, waiting times, and Kidney Donor Profile Index (KDPI) of transplanted kidneys. Transplant rates were not statistically different before and after KAS implementation for either prevalent (2.37 vs. 2.29, relative risk [RR] 0.96; 95% confidence interval [CI] 0.62-1.49) or incident (4.76 vs. 4.36, RR 0.92; 95% CI 0.53-1.60) candidates. Median waiting time (MWT) to deceased donor kidney transplant for prevalent PLDs in the post-KAS cohort was 102.6 days compared with 82.3 days in the pre-KAS cohort (p = 0.98). The median KDPI for PLD recipients was 31% with KAS versus 23% before KAS (p = 0.02). Despite a sharp decrease in the MWT for highly prioritized candidates with calculated panel reactive antibodies of 98-100% (from >7000 to 1164 days), PLDs still had much shorter waiting times (MWT 102.6 days). The new system continues to provide quick access to high-quality organs for PLDs.


Asunto(s)
Asignación de Recursos para la Atención de Salud , Trasplante de Hígado/mortalidad , Donadores Vivos , Obtención de Tejidos y Órganos/métodos , Receptores de Trasplantes , Adulto , Anciano , Aloinjertos , Cadáver , Femenino , Supervivencia de Injerto , Prueba de Histocompatibilidad , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Listas de Espera
4.
Am J Transplant ; 16(6): 1834-47, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-26932731

RESUMEN

After over a decade of discussion, analysis, and consensus-building, a new kidney allocation system (KAS) was implemented on December 4, 2014. Key goals included improving longevity matching between donor kidneys and recipients and broadening access for historically disadvantaged subpopulations, in particular highly sensitized patients and those with an extended duration on dialysis but delayed referral for transplantation. To evaluate the early impact of KAS, we compared Organ Procurement and Transplantation Network data 1 year before versus after implementation. The distribution of transplants across many recipient characteristics has changed markedly and suggests that in many ways the new policy is achieving its goals. Transplants in which the donor and recipient age differed by more than 30 years declined by 23%. Initial, sharp increases in transplants were observed for Calculated Panel-Reactive Antibody 99-100% recipients and recipients with at least 10 years on dialysis, with a subsequent tapering of transplants to these groups suggesting bolus effects. Although KAS has arguably increased fairness in allocation, the potential costs of broadening access must be considered. Kidneys are more often being shipped over long distances, leading to increased cold ischemic times. Delayed graft function rates have increased, but 6-month graft survival rates have not changed significantly.


Asunto(s)
Funcionamiento Retardado del Injerto/epidemiología , Selección de Donante , Implementación de Plan de Salud , Trasplante de Riñón , Donantes de Tejidos/provisión & distribución , Obtención de Tejidos y Órganos/legislación & jurisprudencia , Obtención de Tejidos y Órganos/métodos , Adolescente , Adulto , Anciano , Cadáver , Niño , Preescolar , Femenino , Regulación Gubernamental , Supervivencia de Injerto , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Estados Unidos/epidemiología , Adulto Joven
5.
Am J Transplant ; 16(6): 1707-14, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-26813036

RESUMEN

The Organ Procurement and Transplantation Network (OPTN) Deceased Donor Potential Study, funded by the Health Resources and Services Administration, characterized the current pool of potential deceased donors and estimated changes through 2020. The goal was to inform policy development and suggest practice changes designed to increase the number of donors and organ transplants. Donor estimates used filtering methodologies applied to datasets from the OPTN, the National Center for Health Statistics, and the Agency for Healthcare Research and Quality and used these estimates with the number of actual donors to estimate the potential donor pool through 2020. Projected growth of the donor pool was 0.5% per year through 2020. Potential donor estimates suggested unrealized donor potential across all demographic groups, with the most significant unrealized potential (70%) in the 50-75-year-old age group and potential Donation after Circulatory Death (DCD) donors. Actual transplants that may be realized from potential donors in these categories are constrained by confounding medical comorbidities not identified in administrative databases and by limiting utilization practices for organs from DCD donors. Policy, regulatory, and practice changes encouraging organ procurement and transplantation of a broader population of potential donors may be required to increase transplant numbers in the United States.


Asunto(s)
Muerte Encefálica , Política de Salud , Trasplante de Órganos , Donantes de Tejidos/provisión & distribución , Obtención de Tejidos y Órganos/estadística & datos numéricos , Adolescente , Adulto , Anciano , Cadáver , Niño , Preescolar , Bases de Datos Factuales , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Estados Unidos , United States Health Resources and Services Administration , Adulto Joven
6.
Am J Transplant ; 15(12): 3123-33, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26560245

RESUMEN

Analysis and dissemination of transplant patient safety data are essential to understanding key issues facing the transplant community and fostering a "culture of safety." The Organ Procurement and Transplantation Network's (OPTN) Operations and Safety Committee de-identified safety situations reported through several mechanisms, including the OPTN's online patient safety portal, through which the number of reported cases has risen sharply. From 2012 to 2013, 438 events were received through either the online portal or other reporting pathways, and about half were self-reports. Communication breakdowns (22.8%) and testing issues (16.0%) were the most common types. Events included preventable errors that led to organ discard as well as near misses. Among events reported by Organ Procurement Organization (OPOs), half came from just 10 of the 58 institutions, while half of events reported by transplant centers came from just 21 of 250 institutions. Thirteen (23%) OPOs and 155 (62%) transplant centers reported no events, suggesting substantial underreporting of safety-related errors to the national database. This is the first comprehensive, published report of the OPTN's safety efforts. Our goals are to raise awareness of safety data recently reported to the OPTN, encourage additional reporting, and spur systems improvements to mitigate future risk.


Asunto(s)
Bases de Datos Factuales , Trasplante de Órganos , Seguridad del Paciente/normas , Obtención de Tejidos y Órganos/tendencias , Comunicación , Recolección de Datos , Humanos , Sistema de Registros , Estados Unidos
7.
Am J Transplant ; 11(9): 1943-50, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21812917

RESUMEN

The association of serum uric acid (UA) with kidney transplant outcomes is uncertain. We examined the predictive value of UA during the first year posttransplant as a time-varying factor for graft survival after adjustment for time-dependent and independent confounding factors. Four hundred and eighty-eight renal allograft recipients transplanted from January 2004 to June 2006 and followed for 41.1 ± 17.7 months were included. Data on UA, estimated glomerular filtration rate (eGFR), tacrolimus level, mycophenolate mofetil (MMF) and prednisone doses, use of allopurinol, angiotensin-converting enzyme-inhibitor/angiotensin-receptor-blocker (ACEi/ARB) and diuretics at 1, 3, 6, 9 and 12 months were collected. Primary endpoint of the study was graft loss, defined as graft failure and death. Cox proportional hazard models and generalized estimating equations were used for analysis. UA level was associated with eGFR, gender, retransplantation, decease-donor organ, delayed graft function, diuretics, ACEi/ARB and MMF dose. After adjustment for these confounders, UA was independently associated with increased risk of graft loss (HR: 1.15, p = 0.003; 95% CI: 1.05-1.27). Interestingly, UA interacted with eGFR (HR: 0.996, p < 0.05; 95% CI: 0.993-0.999 for interaction term). Here, we report a significant association between serum UA during first year posttransplant and graft loss, after adjustment for corresponding values of time-varying variables including eGFR, immunosuppressive drug regimen and other confounding factors. Its negative impact seems to be worse with lower eGFR.


Asunto(s)
Supervivencia de Injerto , Trasplante de Riñón , Ácido Úrico/sangre , Adulto , Anciano , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales
8.
Am J Transplant ; 11(9): 1792-802, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21812920

RESUMEN

The first Banff proposal for the diagnosis of pancreas rejection (Am J Transplant 2008; 8: 237) dealt primarily with the diagnosis of acute T-cell-mediated rejection (ACMR), while only tentatively addressing issues pertaining to antibody-mediated rejection (AMR). This document presents comprehensive guidelines for the diagnosis of AMR, first proposed at the 10th Banff Conference on Allograft Pathology and refined by a broad-based multidisciplinary panel. Pancreatic AMR is best identified by a combination of serological and immunohistopathological findings consisting of (i) identification of circulating donor-specific antibodies, and histopathological data including (ii) morphological evidence of microvascular tissue injury and (iii) C4d staining in interacinar capillaries. Acute AMR is diagnosed conclusively if these three elements are present, whereas a diagnosis of suspicious for AMR is rendered if only two elements are identified. The identification of only one diagnostic element is not sufficient for the diagnosis of AMR but should prompt heightened clinical vigilance. AMR and ACMR may coexist, and should be recognized and graded independently. This proposal is based on our current knowledge of the pathogenesis of pancreas rejection and currently available tools for diagnosis. A systematized clinicopathological approach to AMR is essential for the development and assessment of much needed therapeutic interventions.


Asunto(s)
Autoanticuerpos/inmunología , Rechazo de Injerto/diagnóstico , Trasplante de Páncreas/inmunología , Guías de Práctica Clínica como Asunto , Rechazo de Injerto/inmunología , Humanos
9.
Histol Histopathol ; 25(2): 189-96, 2010 02.
Artículo en Inglés | MEDLINE | ID: mdl-20017105

RESUMEN

Sirolimus is associated with prolonged delayed graft function (DGF) following renal transplantation and exacerbation of proteinuria. We assessed renal allograft biopsies from DGF patients treated with de novo sirolimus (n = 10) for renal tubular cell and podocyte apoptosis and expression of activated caspase-3, Bcl-2, and mTOR and compared them to biopsies from DGF patients not receiving sirolimus (n = 15). Both groups received mycophenolate mofetil, prednisone and antibody induction. Apoptosis was assessed using terminal deoxynucleodidyl transferase mediated dUTP nick end labeling (TUNEL) staining. Caspase-3, Bcl-2, and mTOR expression were assessed by immunohistochemistry. Sirolimus treated patients had 334+/-69 TUNEL positive cells per 5 high power fields compared to 5.5+/-2.9 TUNEL positive cells in control patients (p<0.001). The number of TUNEL positive cells correlated with tubular architectural disruption. Expression of activated caspase-3, Bcl-2, or activated mTOR did not differ between groups. 60% of biopsies from sirolimus treated patients compared to 7% of biopsies from controls showed diffuse podocyte apoptosis (p = 0.007). There was no podocyte expression of activated mTOR, activated caspase-3, or Bcl-2 in either group. These data suggest that DGF patients treated with sirolimus have increased renal tubular cell apoptosis and podocyte apoptosis.


Asunto(s)
Apoptosis/efectos de los fármacos , Funcionamiento Retardado del Injerto/inducido químicamente , Células Epiteliales/efectos de los fármacos , Inmunosupresores/efectos adversos , Trasplante de Riñón/efectos adversos , Túbulos Renales/efectos de los fármacos , Podocitos/efectos de los fármacos , Sirolimus/efectos adversos , Adulto , Biopsia , Caspasa 3/análisis , Funcionamiento Retardado del Injerto/metabolismo , Funcionamiento Retardado del Injerto/patología , Quimioterapia Combinada , Células Epiteliales/química , Células Epiteliales/patología , Femenino , Humanos , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Péptidos y Proteínas de Señalización Intracelular/análisis , Túbulos Renales/química , Túbulos Renales/patología , Masculino , Persona de Mediana Edad , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapéutico , Podocitos/química , Podocitos/patología , Prednisona/uso terapéutico , Proteínas Serina-Treonina Quinasas/análisis , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Estudios Retrospectivos , Serina-Treonina Quinasas TOR , Trasplante Homólogo , Resultado del Tratamiento
10.
Am J Transplant ; 8(6): 1237-49, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18444939

RESUMEN

Accurate diagnosis and grading of rejection and other pathological processes are of paramount importance to guide therapeutic interventions in patients with pancreas allograft dysfunction. A multi-disciplinary panel of pathologists, surgeons and nephrologists was convened for the purpose of developing a consensus document delineating the histopathological features for diagnosis and grading of rejection in pancreas transplant biopsies. Based on the available published data and the collective experience, criteria for the diagnosis of acute cell-mediated allograft rejection (ACMR) were established. Three severity grades (I/mild, II/moderate and III/severe) were defined based on lesions known to be more or less responsive to treatment and associated with better- or worse-graft outcomes, respectively. The features of chronic rejection/graft sclerosis were reassessed, and three histological stages were established. Tentative criteria for the diagnosis of antibody-mediated rejection were also characterized, in anticipation of future studies that ought to provide more information on this process. Criteria for needle core biopsy adequacy and guidelines for pathology reporting were also defined. The availability of a simple, reproducible, clinically relevant and internationally accepted schema for grading rejection should improve the level of diagnostic accuracy and facilitate communication between all parties involved in the care of pancreas transplant recipients.


Asunto(s)
Rechazo de Injerto/clasificación , Rechazo de Injerto/patología , Trasplante de Páncreas , Páncreas/patología , Trasplante Homólogo/patología , Biopsia , Rechazo de Injerto/diagnóstico , Humanos
11.
Transplant Proc ; 36(3): 758-9, 2004 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15110653

RESUMEN

Polyoma virus allograft nephropathy often results in accelerated graft loss despite reduction of immunosuppression and/or treatment with antiviral agents. Irreversible renal fibrosis due to late diagnosis is likely to be one of the important causes of treatment failure. Early biopsy in 14 patients resulted in stable graft function after a mean follow-up of 22 months.


Asunto(s)
Trasplante de Riñón/patología , Infecciones por Polyomavirus/patología , Biopsia , Creatinina/sangre , Humanos , Inmunosupresores/uso terapéutico , Trasplante de Riñón/inmunología , Reacción en Cadena de la Polimerasa , Poliomavirus/genética , Poliomavirus/aislamiento & purificación , Resultado del Tratamiento
12.
Transplant Proc ; 36(10): 3028-31, 2004 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-15686687

RESUMEN

Evaluation of urine cytology (UC) for decoy cells and quantitative determinations of viruria (urine viral load [UPCR])and viremia (viral load in blood [VLB]) have been proposed as surrogate markers of polyomavirus allograft nephropathy (PVAN). In this study, we present the experience with the concurrent evaluation of UC, UPCR, and VLB in 349 patients (940 sets of samples). Results were correlated with each other and with a previous, concurrent, or subsequent biopsy diagnosis of PVAN. Patients were followed up for a mean of 27 months posttransplantation. We conclude that both UC and UPCR are useful for screening of renal transplant recipients. Simultaneous performance of both UC and UPCR does not add useful clinical information. In patients with positive UC, performance of UPCR, however, can allow for the distinction between BK and JC polyoma viruses. Quantitative measurement of viremia is not indicated in patients lacking viruria because no patients with PVAN present with this combination of findings. In patients with viruria, a positive viremia strongly correlates with PVAN. Rationale selection of screening protocols based on the current knowledge of the infection and tailored to the available laboratory capabilities in each transplantation center can optimize the use of resources.


Asunto(s)
Trasplante de Riñón/efectos adversos , Trasplante de Riñón/economía , Infecciones por Polyomavirus/economía , Biopsia/economía , Análisis Costo-Beneficio , Estudios de Seguimiento , Humanos , Trasplante de Riñón/patología , Maryland , Infecciones por Polyomavirus/epidemiología , Trasplante Homólogo , Carga Viral , Viremia/economía , Viremia/epidemiología
13.
J Clin Pharmacol ; 41(8): 861-9, 2001 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-11504274

RESUMEN

The study was performed to compare the efficacy and side effects of azathioprine (AZA) and mycophenolate mofetil (MMF) in conjunction with cyclosporine or tacrolimus and steroids for the prevention of acute pancreas rejection during the first 6 months of pancreas transplantation. In this case-controlled study, MMF is compared with historical controls of AZA in the prevention of acute pancreas rejection. The primary measures of treatment efficacy were patient and pancreas survival rate at 6 months after transplantation. Secondary efficacy measures were the occurrence of biopsy-proven pancreas rejections and the use of antilymphocyte preparations for rejection treatment. A total of 111 pancreas transplant patients (57 in the AZA group and 54 in the MMF group) were evaluated. The 6-month patient survival rate was 96% in the AZA group versus 97% in the MMF group (p = 0.57). The 6-month pancreas graft survival rate was 88% in the AZA group versus 91% in the MMF group (p = 0.29). However, biopsy-proven rejection episodes during the first 6 months of transplantation were significantly lower with MMF (46%) than with AZA (69%) (p = 0.01). In addition, patients in the AZA group received a greater number of full courses of antilymphocyte therapy as a rejection treatment (p = 0.004). Overall, the frequency of adverse events was similar, although the MMF group experienced higher incidences of gastrointestinal adverse events. In conclusion, compared with AZA, MMF significantly reduces the rate of biopsy-proven pancreas rejection during the first 6 months of transplantation and is well tolerated, except for gastrointestinal adverse events.


Asunto(s)
Azatioprina/uso terapéutico , Rechazo de Injerto/prevención & control , Inmunosupresores/uso terapéutico , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapéutico , Trasplante de Páncreas/inmunología , Enfermedad Aguda , Adulto , Femenino , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Trasplante de Páncreas/mortalidad , Tasa de Supervivencia
14.
Kidney Int ; 59(4): 1567-73, 2001 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-11260422

RESUMEN

BACKGROUND: Chronic allograft nephropathy is the major cause of progressive renal failure in renal transplant recipients. It has no definitive treatment. METHODS: One hundred eighteen renal transplant recipients with declining kidney function and biopsy-proven chronic allograft nephropathy had their cyclosporine or tacrolimus dose reduced or discontinued with either the addition or continuation of mycophenolate mofetil and low-dose steroids at a mean of 853.3 days post-transplantation. Their renal function was modeled before and after this intervention by two methods: A least-square regression was used to assess the decay of renal function after the intervention and to compare that with the slope pre-intervention, whereas a hinge regression line method was used to assess the correlation of the intervention with the inflection point and the impact of the intervention on the decay of renal function. Mean follow-up was 651.0 days after the intervention. Serum creatinine at the time of intervention was 2.8 +/- 0.9 mg/dL in the reduced dose cyclosporine (N = 67) and reduced dose tacrolimus (N = 33) groups, and was 2.7 +/- 0.7 mg/dL in the group with discontinued calcineurin inhibitor (N = 18). RESULTS: Using the least-square method, 91.7% of the no calcineurin inhibitor group, 51.6% of the reduced dose cyclosporine group, and 59.3% of the reduced dose tacrolimus group had improved or lack of deterioration in slope after the intervention. Using the hinge regression line method, there was a statistically significant correlation of the inflection point with the intervention (P = 0.001). Moreover, there was a similar relationship with stabilized or improved graft function observed with the hinge regression line method and the least-square method, as 72.2% of the calcineurin inhibitor withdrawal group, 54.4% of reduced-dose cyclosporine group, and 40% of the reduced-dose tacrolimus group had improved the slope of decay of renal function or lack of deterioration after the inflection point. The difference between the calcineurin inhibitor withdrawal group and the reduced-dose cyclosporine/tacrolimus groups on the decay in renal function was significant (P = 0.038) with the least-square method and nearly significant (P = 0.056) using the hinge regression line method. CONCLUSION: This intervention was safe, well tolerated, and associated with a minimal risk of acute rejection. We conclude that the reduction and possible withdrawal of calcineurin inhibitors may be necessary to slow the rate of loss of renal function in patients with chronic allograft nephropathy and deteriorating renal function.


Asunto(s)
Calcineurina/efectos adversos , Ciclosporina/administración & dosificación , Inmunosupresores/administración & dosificación , Enfermedades Renales/prevención & control , Trasplante de Riñón , Ácido Micofenólico/análogos & derivados , Tacrolimus/administración & dosificación , Corticoesteroides/administración & dosificación , Corticoesteroides/uso terapéutico , Adulto , Enfermedad Crónica , Ciclosporina/efectos adversos , Ciclosporina/uso terapéutico , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Inmunosupresores/uso terapéutico , Riñón/efectos de los fármacos , Riñón/fisiopatología , Enfermedades Renales/inducido químicamente , Enfermedades Renales/fisiopatología , Masculino , Persona de Mediana Edad , Ácido Micofenólico/uso terapéutico , Tacrolimus/efectos adversos , Tacrolimus/uso terapéutico , Factores de Tiempo
15.
Am J Transplant ; 1(4): 373-81, 2001 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-12099383

RESUMEN

The morphological features of polyoma virus disease (PVDz) in 571 concurrent urine and biopsy samples from 413 patients are described. In 54 patients PV was found in both biopsy and urine samples. Histologically, PV presented as: (a) mild, viral cytopathic/cytolytic changes, with absent or minimal inflammation involving isolated tubules; (b) moderate and severe, cytopathic/cytolytic changes associated with patchy or diffuse tubulo-interstitial inflammation and atrophy; (c) advanced, graft sclerosis with rare or absent viral cytopathic changes, indistinguishable from chronic allograft nephropathy. Histological progression from mild to moderate or severe disease was seen in 28 patients. The mean post-transplantation time at diagnosis was similar in patients with mild or moderate-severe renal involvement (1.05 and 1.3 years, respectively). All patients presented with similarly increased values of serum creatinine (mean 1.35 mg/dL). There was strong correlation between the number of PV infected cells in urine and the concurrent biopsies (p = 0.0001). In 13 patients PV was found only in urine; of these, two developed PVDz later. The positive predictive value of a positive urine was 90%, the negative predictive value of a negative urine was 99% and the accuracy of the test was 97%. We conclude that urine cytology is useful to evaluate renal transplant patients with PV reactivation because sloughed tubular cells are found in urine and positive urine samples are a consistent manifestation of PV renal involvement.


Asunto(s)
Trasplante de Riñón , Infecciones por Polyomavirus/diagnóstico , Complicaciones Posoperatorias/virología , Atrofia , Biopsia , Progresión de la Enfermedad , Humanos , Inflamación , Trasplante de Riñón/patología , Túbulos Renales/patología , Túbulos Renales/virología , Donadores Vivos , Infecciones por Polyomavirus/orina , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios Retrospectivos , Trasplante Homólogo , Orina/citología
16.
Curr Hypertens Rep ; 2(5): 473-7, 2000 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-10995523

RESUMEN

Renal transplantation is the treatment of choice for many patients with endstage renal disease. Patient survival is improved compared with dialysis for all patient ages and racial groups. Renal allograft survival is closely connected with recipient blood pressure. Blood pressure treatment goals that improve patient outcome have been defined for patients with nontransplant renal disease but not for patients with renal transplants. Extrapolating from data from nonrenal transplant patients suggests that aggressive treatment of hypertension in renal transplant patients may improve allograft and patient survival.


Asunto(s)
Hipertensión/tratamiento farmacológico , Trasplante de Riñón , Antihipertensivos/uso terapéutico , Ciclosporina/uso terapéutico , Supervivencia de Injerto , Humanos , Hipertensión/fisiopatología , Inmunosupresores/uso terapéutico , Trasplante de Riñón/fisiología , Periodo Posoperatorio , Proteinuria/fisiopatología
17.
Transplantation ; 69(9): 1968-71, 2000 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-10830244

RESUMEN

BACKGROUND: Cytomegalovirus (CMV) infection is a common problem in solid organ transplant recipients. CMV infection of pancreas allografts is not, however, well described. METHODS: We report the clinical presentation, histologic findings, treatment, and outcome in four patients with CMV allograft pancreatitis. These patients presented 18 weeks to 44 months after transplantation with elevated serum amylase and lipase and were suspected to have acute rejection. Percutaneous pancreas allograft biopsy specimens showed evidence of tissue invasive CMV infection. One patient had simultaneous CMV infection and acute rejection. RESULTS: Prolonged treatment with ganciclovir resulted in clinical and histologic resolution of the CMV disease. Rejection was successfully treated. Primary CMV infection in seronegative recipients seemed to be a risk factor. Three patients maintain normal allograft function; one patient lost function due to chronic rejection. The histology of tissue-invasive CMV pancreas allograft infection and its differentiation from acute rejection is described. CONCLUSION: Prompt diagnosis and prolonged therapy with antiviral agents can result in maintenance of allograft function.


Asunto(s)
Infecciones por Citomegalovirus/diagnóstico , Trasplante de Páncreas/efectos adversos , Pancreatitis/diagnóstico , Adulto , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/patología , Femenino , Rechazo de Injerto , Humanos , Masculino , Páncreas/patología , Pancreatitis/tratamiento farmacológico , Pancreatitis/patología , Trasplante Homólogo
18.
Transplantation ; 68(3): 396-402, 1999 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-10459544

RESUMEN

BACKGROUND: The introduction of the potent immunosuppressive drugs tacrolimus (FK) and cyclosporine (CSA) has markedly improved the outcome of solid organ transplantation. However, these drugs can cause posttransplantation diabetes mellitus. Abnormalities in the glucose metabolism are of particular significance in pancreas transplantation. METHODS: We studied 26 pancreas allograft biopsies, performed 1-8 months posttransplantation, from 20 simultaneous kidney-pancreas transplant recipients, randomized to receive either FK or CSA. The biopsies were studied by light microscopy, immunoperoxidase stains for insulin and glucagon, in situ DNA-end labeling for detection of apoptosis, and electron microscopy. The islet morphology was correlated with the mean and peak levels of CSA and FK in serum, with corticosteroid administration and with glycemia. RESULTS: On light microscopy cytoplasmic swelling, vacuolization, apoptosis, and abnormal immunostaining for insulin were seen in biopsies from patients receiving either FK or CSA. The islet cell damage was more frequent and severe in the group receiving FK than in the group receiving CSA (10/13 and 5/13, respectively) but the differences were not statistically significant. Significant correlation was seen between the presence of islet cell damage and serum levels of CSA or FK during the 15 days previous to the biopsy, as well as with the peak level of FK. Toxic levels of CSA or FK and administration of pulse steroids were associated with hyperglycemia when these occurred concurrently (P=0.005). Toxic levels of CSA or FK by themselves were associated with hyperglycemia in a minority of cases (8 and 26%, respectively). Electron microscopy showed cytoplasmic swelling and vacuolization, and marked decrease or absence of dense-core secretory granules in beta cells; the changes were more pronounced in patients on FK. Serial biopsies from two hyperglycemic patients receiving FK and evidence of islet cell damage demonstrated reversibility of the damage when FK was discontinued. CONCLUSIONS: The structural damage to beta cells demonstrated in this study is similar to morphological and functional abnormalities previously described in experimental animal models and can at least partially account for the glucose metabolism abnormalities seen in patients receiving these drugs. Toxic levels of CSA or FK and higher steroid doses potentiate each others' diabetogenic effects.


Asunto(s)
Ciclosporina/farmacología , Inmunosupresores/farmacología , Islotes Pancreáticos/efectos de los fármacos , Tacrolimus/farmacología , Adulto , Biopsia , Ciclosporina/toxicidad , Femenino , Estudios de Seguimiento , Humanos , Hiperglucemia/inducido químicamente , Hiperglucemia/etiología , Hiperplasia , Inmunosupresores/toxicidad , Islotes Pancreáticos/patología , Masculino , Microscopía Electrónica , Persona de Mediana Edad , Trasplante de Páncreas/patología , Tacrolimus/toxicidad , Factores de Tiempo , Trasplante Homólogo/patología , Vacuolas/metabolismo
19.
Hum Pathol ; 30(8): 970-7, 1999 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-10452511

RESUMEN

Human polyoma virus (PV) interstitial nephritis occurs in immunosuppressed patients after reactivation of latent virus in renal epithelium. Currently, there is neither general consensus about the incidence of clinically significant PV infection in renal transplants nor conclusive evidence determining its significance in the long-term graft outcome. We evaluated 601 renal transplant biopsy specimens (from 365 patients) by routine light microscopy and immunoperoxidase stains with antibody against SV40 (which cross reacts with PV). We also examined urine samples from 200 patients (100 obtained concurrently with a renal biopsy in patients presenting with acute graft dysfunction and 100 from patients with stable graft function). Electron microscopic evaluation was performed in 50 renal biopsy specimens and in 23% of all urine samples. PV was identified in 1.8% biopsy specimens (1.9% of patients). PV interstitial nephritis showed the typical viral cytopathic changes in tubular epithelial cells associated with marked tubular damage and a disproportionately mild degree of tubulitis. There was no difference in the incidence of PV in the urine of patients with acutely deteriorating versus stable renal function (18% and 19%, respectively); however, urines with large numbers of infected cells (> 10/cytospin) and inflammatory changes in the sediments corresponded invariably to patients with acute allograft dysfunction (8 of 8), and in most cases to biopsy specimens showing PV interstitial nephritis (7 of 8). Based on these findings, urine samples seem to be the most sensitive and cost-effective screening method for PV infection; only urine samples with inflamed sediments and abundant infected cells correlate with clinically significant disease. In these cases, examination of a renal biopsy is indicated. Immunohistochemical stains are useful to confirm the presence of PV but do not increase the sensitivity of diagnosis of PV if this is not already suspected on routine light microscopy. In our material, immunostains were helpful ruling out the presence of PV in a small number of biopsy specimens (2%) that showed markedly reactive tubular cells resembling PV infection. Most patients with PV interstitial nephritis responded to decreased immunosuppression; however, the decay in graft function (based on creatinine slopes) was significantly more rapid in these patients than in matched controls. Evidence of PV infection should be systematically sought in renal biopsy specimens and urine samples from renal allograft recipients.


Asunto(s)
Trasplante de Riñón , Riñón/virología , Nefritis Intersticial/virología , Poliomavirus/aislamiento & purificación , Adolescente , Adulto , Anciano , Niño , Femenino , Rechazo de Injerto/patología , Humanos , Riñón/patología , Riñón/ultraestructura , Masculino , Microscopía Electrónica , Persona de Mediana Edad , Nefritis Intersticial/patología , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/orina , Estudios Prospectivos , Infecciones Tumorales por Virus/patología , Infecciones Tumorales por Virus/orina
20.
Transplantation ; 67(5): 722-8, 1999 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-10096529

RESUMEN

BACKGROUND: Laparoscopic donor nephrectomy (laparoNx) has the potential to increase living kidney donation rates by reducing the pain and suffering of the donor. However, renal function outcomes of a large series of recipients of laparoNx have not been studied. METHODS: We retrospectively reviewed the records of 132 recipients of laparoNx done at our center between 3/96 and 11/97 and compared them to 99 recipients of kidneys procured by the open technique (openNx) done between 10/93 and 3/96. RESULTS: Significantly more patients in the laparoNx group (25.2%) were taking tacrolimus within the first month than those in the openNx group (2.1%). Mean serum creatinine was higher in laparoNx compared with openNx at 1 week (2.8+/-0.3 and 1.8+/-0.2 mg/dl, respectively; P=0.005) and at 1 month (2.0+/-0.1 and 1.6+/-0.1 mg/dl, P=0.05) after transplant. However, by 3 and 6 months, the mean serum creatinine was similar in the two groups (1.7+/-0.1 versus 1.5+/-0.05 mg/dl, and 1.7+/-0.1 versus 1.7+/-0.1, respectively). By 1 year posttransplant, the mean serum creatinine for laparoNx was actually less than that for openNx (1.4+/-0.1 and 1.7+/-0.1 mg/dl, P=0.03). Although patients in the laparoNx compared to the openNx group were more likely to have delayed graft function (7.6 versus 2.0%) and ureteral complications (4.5 versus 1.0%), the rate of other complications, as well as hospital length of stay, patient and graft survival rates were similar in the two groups. CONCLUSION: Although laparoNx allografts have slower initial function compared with openNx, there was no significant difference in longer term renal function.


Asunto(s)
Trasplante de Riñón/métodos , Donadores Vivos , Adulto , Creatinina/sangre , Humanos , Inmunosupresores/uso terapéutico , Laparoscopía , Nefrectomía , Estudios Retrospectivos , Tacrolimus/uso terapéutico , Resultado del Tratamiento
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